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BackgroundO'Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O'Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.MethodsAffected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.ResultsWe report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.ConclusionOur study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome.

Introduction: Factor Xa (fXa) inhibitor reversal for life-threatening bleeding is controversial due to a lack of high-quality evidence. The purpose of this study was to determine the hemostatic efficacy of four-factor prothrombin complex concentrate (4F-PCC) for the reversal of fXa inhibitors compared to warfarin for life-threatening bleeding. Methods: This was a multicenter, retrospective cohort study at two academic medical centers between January 1, 2014–December 31, 2019, which included patients who presented to the emergency department with a life-threatening bleed necessitating anticoagulation reversal with 4F-PCC. The primary endpoint was achievement of hemostatic efficacy after 4F-PCC administration. Results: Of the 525 patients who had an order for 4F-PCC during the study period, 148 patients met the criteria for inclusion (n = 48 fXa inhibitor group; n = 100 warfarin group). Apixaban (52.1%) and rivaroxaban (45.8%) were the most commonly used fXa inhibitors. Effective hemostasis was similar between groups (79.2% fXa inhibitor group vs 85% warfarin group, p = 0.38). This was consistent across all types of bleeding. Thrombotic events were rare in both groups (2% vs 3%).  Conclusion: This multicenter, retrospective cohort study demonstrated that using 4F-PCC for treatment of life-threatening bleeding produced effective hemostasis in patients on fXa inhibitors and warfarin.

PurposeHaploinsufficiency of USP7, located at chromosome 16p13.2, has recently been reported in seven individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), seizures, and hypogonadism. Further, USP7 was identified to critically incorporate into the MAGEL2-USP7-TRIM27 (MUST), such that pathogenic variants in USP7 lead to altered endosomal F-actin polymerization and dysregulated protein recycling.MethodsWe report 16 newly identified individuals with heterozygous USP7 variants, identified by genome or exome sequencing or by chromosome microarray analysis. Clinical features were evaluated by review of medical records. Additional clinical information was obtained on the seven previously reported individuals to fully elucidate the phenotypic expression associated with USP7 haploinsufficiency.ResultsThe clinical manifestations of these 23 individuals suggest a syndrome characterized by DD/ID, hypotonia, eye anomalies,feeding difficulties, GERD, behavioral anomalies, and ASD, and more specific phenotypes of speech delays including a nonverbal phenotype and abnormal brain magnetic resonance image findings including white matter changes based on neuroradiologic examination.ConclusionThe consistency of clinical features among all individuals presented regardless of de novo USP7 variant type supports haploinsufficiency as a mechanism for pathogenesis and refines the clinical impact faced by affected individuals and caregivers.

The purpose of this article is to summarize pharmacotherapy related emergency medicine (EM) literature indexed in 2023. Articles were selected utilizing a modified Delphi approach. The table of contents from pre-determined journals were reviewed and independently evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by paired authors. Pharmacotherapy-related publications deemed to be GRADE 1A and 1B were reviewed by the collective group for inclusion in the review. In all, this article summarizes and provides commentary on the potential clinical impact of 13 articles, 6 guidelines, and 5 meta-analyses covering topics including guideline releases and updates on rapid sequence intubation in the critically ill, managing cardiac arrest or life-threatening toxicity due to poisoning, and management of major bleeding following trauma. Also discussed are ongoing controversies surrounding fluid resuscitation, time and treatment modalities for ischemic stroke, steroid use in community-acquired pneumonia, targeted blood product administration, and much more. [ABSTRACT FROM AUTHOR]

Objective: To evaluate practitioner use of ketamine and identify potential barriers to use in acutely and critically ill patients. To compare characteristics, beliefs, and practices of ketamine frequent users and non-users. Methods: An online survey developed by members of the Society of Critical Care Medicine (SCCM) Clinical Pharmacy and Pharmacology Section was distributed to physician, pharmacist, nurse practitioner, physician assistant and nurse members of SCCM. The online survey queried SCCM members on self-reported practices regarding ketamine use and potential barriers in acute and critically ill patients. Results: Respondents, 341 analyzed, were mostly adult physicians, practicing in the United States at academic medical centers. Clinicians were comfortable or very comfortable using ketamine to facilitate intubation (80.0%), for analgesia (77.9%), procedural sedation (79.4%), continuous ICU sedation (65.8%), dressing changes (62.4%), or for asthma exacerbation and status epilepticus (58.8% and 40.4%). Clinicians were least comfortable with ketamine use for alcohol withdrawal and opioid detoxification (24.7% and 23.2%). Most respondents reported "never" or "infrequently" using ketamine preferentially for continuous IV analgesia (55.6%) or sedation (61%). Responses were mixed across dosing ranges and duration. The most common barriers to ketamine use were adverse effects (42.6%), other practitioners not routinely using the medication (41.5%), lack of evidence (33.5%), lack of familiarity (33.1%), and hospital/institutional policy guiding the indication for use (32.3%). Conclusion: Although most critical care practitioners report feeling comfortable using ketamine, there are many inconsistencies in practice regarding dose, duration, and reasons to avoid or limit ketamine use. Further educational tools may be targeted at practitioners to improve appropriate ketamine use. [ABSTRACT FROM AUTHOR]

Clinical pharmacists practicing in academia have access to resources and pathways for professional development that clinical pharmacists practicing outside of academia may lack. With timely concerns of premature attrition and burnout in the clinical pharmacy profession, it is critical that employers and professional organizations help meet the professional development needs of clinical pharmacists practicing in outside of academia. Implementation of career ladders, creation of hybrid leadership‐practice positions, achievement of operational excellence, cultivation of a positive culture, and development of optimal metrics may all help employers meet these needs. Professional organizations are called on to provide clinical pharmacists with a clear path for advancement within the organization to contribute to their ongoing professional development; this centers on the development of mentorship programs and opportunities to expand the professional portfolio of the clinical pharmacist practicing outside of academia. It is imperative that employers and professional organizations address the lack of existing career advancement and professional development opportunities to combat the premature attrition of clinical pharmacists from practice, improve the "life span" of the clinical pharmacist, and ultimately maintain the clinical pharmacy profession as a whole. [ABSTRACT FROM AUTHOR]

The article discusses the challenges of implementing a research model in the field of pharmacy, as outlined by the American College of Clinical Pharmacy (ACCP). A survey conducted by the ACCP found that there is a disparity between the importance placed on research and the support provided for it. The Mayo Clinic is presented as an example of a health system that has successfully built institutional support for pharmacy research, resulting in a significant increase in publication rates. However, there are barriers preventing other institutions from replicating this model, including constraints on institutional support, time, funding, and skills. The article emphasizes the need for more efforts to support clinical pharmacists in research and calls for improvements in research training for early-career pharmacists. [Extracted from the article]

The preferred vasopressor in post-cardiac arrest shock has not been established with robust clinical outcomes data. Our goal was to perform a systematic review and meta-analysis comparing rates of in-hospital mortality, refractory shock, and hemodynamic parameters in post-cardiac arrest patients who received either norepinephrine or epinephrine as primary vasopressor support. We conducted a search of PubMed, Cochrane Library, and CINAHL from 2000 to 2022. Included studies were prospective, retrospective, or published abstracts comparing norepinephrine and epinephrine in adults with post-cardiac arrest shock or with cardiogenic shock and extractable post-cardiac arrest data. The primary outcome of interest was in-hospital mortality. Other outcomes included incidence of arrhythmias or refractory shock. The database search returned 2646 studies. Two studies involving 853 participants were included in the systematic review. The proposed meta-analysis was deferred due to low yield. Crude incidence of in-hospital mortality was numerically higher in the epinephrine group compared with norepinephrine in both studies, but only statistically significant in one. Risk of bias was moderate to severe for in-hospital mortality. Additional outcomes were reported differently between studies, minimizing direct comparison. The vasopressor with the best mortality and hemodynamic outcomes in post-cardiac arrest shock remains unclear. Randomized studies are crucial to remedy this. [ABSTRACT FROM AUTHOR]

While connections between children's sleep and their daytime functioning are well established, less is known about the microstructural features of sleep that support emotional wellbeing. Investigating these relationships in healthy children may provide insight into adaptive emotional development. We therefore examined associations between non-rapid eye movement (N2) sleep spindles and both state- and trait-based measures of emotion. A sample of 30 children (7–11 years) without psychiatric disorders completed a baseline assessment, one night of at-home polysomnography (PSG), and an in-lab emotional state assessment the next day including self-reported arousal in response to affective images. Trait-based measures of anxiety and depression as well as savoring, a positive emotion regulatory strategy, were also completed. N2 sleep spindle parameters, including spindle density (number/min) and peak frequency in central regions, were detected using an automated algorithm. Greater spindle density was significantly associated with decreased state-based emotional arousal towards negative affective images, and greater spindle peak frequency was associated with greater trait-based use of savoring. However, neither spindle parameter was associated with child anxiety or depressive symptoms. Findings align with and expand on prior research to suggest that N2 sleep spindles support adaptive emotional functioning in school-aged children. • We examined sleep spindles and emotional functioning in healthy school-aged children. • Greater spindle density was associated with less arousal towards negative affective images. • Higher spindle peak frequency correlated with savoring, a positive emotion regulatory strategy. • Spindles were unassociated with symptoms of anxiety and depression. • Spindles may provide a general marker of emotional regulatory capacity in childhood. [ABSTRACT FROM AUTHOR]